Calorie restriction (CR) is the most potent, non-pharmacological intervention to support metabolic health. The effects of calorie restriction exceed weight loss. Consistent throughout many studies, calorie restriction induces a reduction in energy expenditure that is larger than the loss of metabolic mass, i.e. fat-free mass and fat mass, can explain. Per prevailing theories of mammalian aging, this disproportionate reduction in metabolic rate, defined as metabolic adaptation, reduces oxidative damage and thereby delays age-associated declines in physiological function. The aim of this narrative review is to investigate the origins of CR-induced metabolic adaptation. From a physiological standpoint this likely relates to the composition of body weight loss, reductions in insulin secretion, thyroid and leptin concentrations, and increased mitochondrial energy efficiency. Behavioral factors including physical activity and eating behaviors likely also play a role, specifically to prevent weight regain. Future studies are required to understand the interindividual differences in the response to CR, e.g. by sex, physical activity, or mitochondrial capacity, and to assess the long-term implications of CR for weight regain. •Changes in fat-free mass composition explain part of the metabolic adaptation with calorie restriction.•Insulin secretion, thyroid hormones and leptin associate with metabolic adaptation.•Changes in physical activity are variable and may affect fat-free mass.•Satiety and activity may be more relevant to weight regain then metabolic rate.